POS0622 BIFIDOBACTERIUM LONGUM RAPO AMELIORATES DERMAL AND PULMONARY FIBROSIS THROUGH THE MODULATION OF GUT MICROBIOTA AND IMMUNE RESPONSE IN BLEOMYCIN-INDUCED SYSTEMIC SCLEROSIS IN MICE
Authors: H. Lee, H. J. Park, D. Yu, S. T. Hong, J. Lee, S. J. Park, M. S. Park, M. Kim, S. Kim, S. I. Lee
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized by immune abnormalities, vasculopathy, and fibrosis of the internal organs[1]. Because the etiology of SSc is uncertain, drugs that improve the course of the disease and symptom are lacking. Recent data have highlighted the importance of the microbiome and its relevance to SSc. The microbiome can trigger an exacerbation of SSc. On the other hand, it may relieve symptoms. <i>Lactobacillus</i> and <i>Bifidobacterium</i> strains have been reported to alleviate gastrointestinal symptoms of SSc[2,3]. However, there are no study on the microbiome that improves the major symptoms of SSc, such as dermal and lung fibrosis. <h3>Objectives</h3> This study aims to screen SSc-associated microbiome at the species level using serum and to explore potential microbial targets for SSc treatment. And we evaluated whether the candidate microbial species ameliorate dermal and lung fibrosis. <h3>Methods</h3> We performed an immunoglobulin (Ig) M antibody microarray against 384 microbial species in the serum from SSc patients and healthy control (HC). Then, the antifibrotic effect of candidate microbial species was investigated using a bleomycin (BLM)-induced fibrosis model in mice. <h3>Results</h3> <i>Bifidobacterium (B.) longum</i> RAPO, which was less abundant in the serum of patients with SSc than HC, alleviated BLM-induced skin and lung fibrosis in mice. The administration of <i>B. longum</i> RAPO normalized fecal microbial diversity with an increase in short-chain fatty acid-producing bacteria. Moreover, infiltrated inflammatory monocytes or macrophages in the spleen, the skin, and bronchoalveolar lavage of BLM-injected mice were significantly reduced by treating <i>B. longum</i> RAPO. In vitro, <i>B. longum</i> RAPO downregulated LPS-induced inflammatory cytokines gene expression in mouse macrophage cell Raw 264.7. <h3>Conclusion</h3> <i>B. longum</i> RAPO could have an antifibrotic effect on skin and lung fibrosis through gut microbial restoration and macrophage regulation in BLM-induced fibrosis mice. Microbial intervention would be a potential option for SSc treatment. <h3>References</h3> [1]Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017 Oct 7;390(10103):1685-1699. doi: 10.1016/S0140-6736(17)30933-9. Epub 2017 Apr 13. PMID: 28413064. [2]Frech TM, Khanna D, Maranian P, Frech EJ, Sawitzke AD, Murtaugh MA. Probiotics for the treatment of systemic sclerosis-associated gastrointestinal bloating/ distention. Clin Exp Rheumatol. 2011 Mar-Apr;29(2 Suppl 65):S22-5. Epub 2011 May 12. PMID: 21586214. [3]Marietta E. V., Murray J. A., Luckey D. H., Jeraldo P. R., Lamba A., Patel R., et al. (2016). Suppression of Inflammatory Arthritis by Human Gut-DerivedPrevotella Histicolain Humanized Mice. Arthritis Rheumatol. 68 (12), 2878–2888. 10.1002/art.39785 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.